Exploring the impact of nano-Se and nano-clay feed supplements on interleukin genes, immunity and growth rate in European Sea Bass (Dicentrarchus labrax).

This study aimed to investigate the effects of adding Nano-Selenium (NSe) and Nano-clay (NC) as feed supplements on European Sea Bass (Dicentrarchus labrax). Two separate experiments were conducted, one with NC and the other with NSe. Each experiment consisted of four sub-groups with varying concentrations of NC or NSe. The expression levels of five immune-related genes (TNF-α, TNF-ß, IL-2, IL-6 and IL-12) were measured using Real-time Quantitative PCR (Rt-PCR) Assay. The results showed an increase in the expression of interleukins (IL-2, IL-6 and IL-12) and pro-inflammatory cytokines (TNF-α and TNF-ß) after exposure to NC and NSe. TNF-α gene expression was significantly higher with both 1 mg and 10 mg concentrations of NC and NSe. TNF-ß gene expression was highest with the 5 mg concentration of NC. The concentrations of 1 mg and 10 mg for NC, and 1 mg, 5 mg, and 10 mg for NSe, led to the highest (p < 0.05) levels of IL-2 expression compared to the control. Similar trends were observed for IL-6 and IL-12 gene expression. Understanding the impact of these concentrations on gene expression, growth rate, biochemical indices, and antioxidant status can provide valuable insights into the potential applications of NC and NSe supplements on European Sea Bass.

Polymorphisms in Lymphotoxin-Alpha as the "Missing Link" in Prognosticating Favourable Response to Omega-3 Supplementation for Dry Eye Disease: A Narrative Review.

Elements of inflammation are found in almost all chronic ocular surface disease, such as dry eye disease. The chronicity of such inflammatory disease speaks to the dysregulation of innate and adaptive immunity. There has been a rising interest in omega-3 fatty acids to attenuate inflammation. While many cell-based (in vitro) studies verify the anti-inflammatory effects of omega-3, different human trials report discordant outcomes after supplementation. This may be due to underlying inter-individual differences in inflammatory cytokine metabolism (such as tumor necrosis factor alpha (TNF-α)), in which genetic differences might play a role, such as polymorphisms in the lymphotoxin alpha (LT-α) gene. Inherent TNF-α production affects omega-3 response and is also associated with LT-α genotype. Therefore, LT-α genotype might predict omega-3 response. Using the NIH dbSNP, we analyzed the relative frequency of LT-α polymorphisms among various ethnicities, each weighted by the genotype's probability of positive response. While the probability of response for unknown LT-α genotypes are 50%, there is greater distinction in response rates between various genotypes. Hence, there is value in genetic testing to prognosticate an individual's response to omega-3.

Effect of Enhanced Recovery after Surgery with Integrated Traditional Chinese and Western Medicine on Postoperative Stress Response of Patients with Gastrointestinal Tumors.

Objective: To investigate the effect of enhanced recovery after surgery (ERAS) with integrated traditional Chinese and Western medicine on postoperative stress response of patients suffering from gastrointestinal tumors. Methods: A total of 74 patients with gastrointestinal tumors who underwent surgical treatment in our hospital from April 2019 to March 2021 were recruited and randomized into the control group and the observation group (1 : 1). The control group received routine treatment and care, while the observation group received ERAS plus integrated traditional Chinese and Western medicine. Clinical observation was performed regarding changes in preoperative mood and postoperative pain level in each group. Changes in expression levels of plasma cortisol, C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-ß (TNF-ß) before and after surgery were detected in each group. Time of patients' first fart and defecation and complications after surgery in each group were recorded. Results: The visual analogue scale (VAS) of patients in the observation group after 12 and 24 h of surgery was significantly lower than that in the control group (12 h: observation group 2.0 (1.00, 3.00) vs. control group 4.00 (3.00, 5.00), p = 0.001; 24 h: observation group 2.00 (1.00, 3.00) vs. control group 3.00 (2.00, 5.00), p = 0.005). The preoperative anxiety degree of patients in the two groups was not statistically significant (p = 0.489). The plasma cortisol level of patients in the observation group after 24 and 48 h of surgery was significantly lower than that in the control group (24 h: observation group 426.54 ± 52.15 nmol/L vs. control group 508.32 ± 41.08 nmol/L, p = 0.001; 48 h: observation group 287.19 ± 44.24 nmol/L vs. control group 362.57 ± 43.46 nmol/L, p = 0.001). Patients' postoperative CRP, IL-6, IL-8, and TNF-ß expression levels in the observation group were remarkably lower than those in the control group at all time points. The first postoperative defecation came earlier in the observation group than that in the control group (observation group 76.00 h (64.50, 87.50) vs. control group 89.00 h (73.50, 116.00), p = 0.007). There was 1 postoperative urinary tract infection in the observation group and 1 postoperative intestinal obstruction and 1 incisional wound infection in the control group. Conclusion: ERAS with integrated traditional Chinese and Western medicine could effectively reduce the postoperative stress response and inflammatory reaction in patients with gastrointestinal tumors, contributing to the safe and quick recovery of gastrointestinal functions of patients.

Eficacia y seguridad de ustekinumab y secukinumab en pacientes adultos con psoriasis vulgar severa, con falla terapéutica a terapia sistémica convencional, fototerapia y terapia biológica con antagonistas del factor de necrosis tumoral disponibles en EsSalud / Efficacy and safety of ustekinumab and secukinumab in adult patients with severe psoriasis vulgaris, with therapeutic failure to conventional systemic therapy, phototherapy and biological therapy with tumor necrosis factor antagonists available in EsSalud

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de ustekinumab y secukinumab para el tratamiento de pacientes adultos con psoriasis vulgar severa, con falla terapéutica a terapia sistémica convencional, fototerapia y terapia biológica con antagonistas del factor de necrosis tumoral (anti-FNT) disponibles, en comparación con la mejor terapia de soporte paliativo (MTSP). La psoriasis es la enfermedad auto inflamatoria crónica dermatológica más frecuente, la cual tiene una prevalencia cercana al 2.5 % en el Perú. La psoriasis vulgar es la forma clínica más común, la cual puede clasificarse, según la severidad, en leve, moderada y severa, de acuerdo a los instrumentos de medición clínica, tales como el Psoriasis Area and Severity Index (PASI), el Dermatology Life Quality Index (DLQI) y el grado de afectación de la superficie corporal total (SCT). La psoriasis severa se define como aquella que cuenta con un PASI ≥ 10, o un DLQI ≥ 10 o la afectación ≥ 10 % del área de SCT. La importancia clínica de la clasificación de acuerdo a la severidad de la psoriasis radica en el tratamiento, el cual requiere de medidas sistémicas para las formas severas. El Petitorio Farmacológico de EsSalud cuenta con terapia tópica, fototerapia, y terapia sistémica convencional (i. e. metotrexato, ciclosporina y acitretina), para el tratamiento de pacientes con psoriasis vulgar severa. Luego de falla terapéutica a los tratamientos mencionados, se cuenta con terapia biológica con los antagonistas del factor de necrosis tumoral (anti-FNT), tales como infliximab, etanercept y adalimumab. La mejor terapia de soporte paliativa (MTSP) se utiliza en los pacientes con psoriasis vulgar severa que presentan falla terapéutica a todos los tratamientos antes mencionados, y consiste en el uso de terapia tópica, fototerapia y terapia sistémica convencional de forma paliativa. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva y jerárquica de la literatura con respecto a la eficacia y seguridad de ustekinumab y secukinumab para el tratamiento de pacientes adultos con psoriasis vulgar severa con falla terapéutica a terapia tópica, fototerapia, terapia sistémica convencional y terapia biológica anti-FNT (i. e. infliximab, etanercept, y adalimumab); comparados con el placebo o la MTSP. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como FDA, EMA y DIGEMID en el Perú. Además, se realizó una búsqueda sistemática en las principales bases de datos, tales como MEDLINE vía PubMed y en Cochrane Library. Asimismo, se realizó una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica y/o evaluación de tecnologías sanitarias: National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Haute Authorité de Santé (HAS), la Institute for Quality and Efficiency in Health Care (IQWiG), la Institute for Clinical and Economic Review (ICER) y el Ministerio de Salud del Perú (MINSA). Además, se realizó una búsqueda de las guías de las principales sociedades o instituciones especializadas en dermatología y en psoriasis, tales como la American Academy of Dermatology (AAD), la British Association of Dermatologists (BAD), la European Academy of Dermatology and Venereology (EADV), y la International Psoriasis Council (IPC). Por último, se buscaron ensayos clínicos en desarrollo o que no hayan sido publicados en la página web www.clinicaltrials.gov que contengan información acerca de las tecnologías evaluadas, y así disminuir el sesgo de publicación. RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de ustekinumab y secukinumab como tratamiento de pacientes adultos con psoriasis vulgar severa con falla terapéutica a terapia tópica, fototerapia, terapia sistémica convencional y terapia biológica anti-FNT (i. e. infliximab, etanercept, y adalimumab); comparados con el placebo o la MTSP. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). Los ECA fueron agrupados en tres comparaciones: (i) ustekinumab vs. placebo o la MTSP; (ii) secukinumab vs. placebo o la MTSP; (iii) secukinumab vs. ustekinumab. CONCLUSIONES: El presente dictamen evaluó la evidencia científica disponible a la actualidad en relación a la eficacia y seguridad de secukinumab y ustekinumab comparados con la MTSP y el placebo en pacientes adultos con psoriasis vulgar severa con falla terapéutica a terapia tópica, fototerapia, terapia sistémica convencional, y terapia biológica anti-FNT disponibles en EsSalud, en términos de PASI 75, DLQI, SCT, y EA. Nuestra revisión de la evidencia disponible hasta agosto del 2019, agrupadas en tres comparaciones (ustekinumab vs. placebo, secukinumab vs. placebo y secukinumab vs. ustekinumab) permitió identificar una GPA de la BAD del Reino Unido y nueve ECA como las principales fuentes de información para la evaluación de los efectos de secukinumab y ustekinumab en nuestra población de interés. El Equipo Técnico del IETSI llevó a cabo un MA con los ECA incluidos para derivar las conclusiones del presente dictamen. Respecto a la comparación ustekinumab vs. placebo, se evidenció un balance riesgo beneficio favorable para ustekinumab en la población de la pregunta PICO a corto plazo (12 semanas), en vista que presentó diferencias clínicamente relevantes y estadísticamente significativas respecto al PASI 75, DLQI 0-1 y DLQI, en la población total de los estudios incluidos. Además, ustekinumab mostró un similar riesgo de presentar EAT, EAS, TII y TIS que el placebo, mientras que presentó un menor riesgo de DT a causa de EA. El MA de la comparación de secukinumab vs. placebo mostró un balance riesgo beneficio favorable para secukinumab en la población de la pregunta PICO a corto plazo (12 semanas), dado que se evidenciaron diferencias clínicamente relevantes y estadísticamente significativas respecto al PASI 75 y DLQI 0-1, a favor de secukinumab, mientras que secukinumab y placebo presentaron un similar riesgo de desenlaces clave de seguridad, tales como EAS, DT por EA y TIS en la población total de los estudios incluidos. Para la comparación de secukinumab vs. ustekinumab, se realizó un MA de los resultados a corto plazo (12 semanas) y se analizaron los resultados del ECA CLEAR a largo plazo (52 semanas). Los resultados de eficacia mostraron que tanto a corto como a largo plazo, las diferencias entre secukinumab y ustekinumab respecto al PASI 75 y al DLQI 0-1 fueron estadísticamente significativas, pero con intervalos de confianza cercanos al punto de no diferencia, y estuvieron sujetas a las limitaciones que presentan los desenlaces de naturaleza subjetiva (PASI y DLQI) que luego de ser ajustadas para convertirlos en desenlaces categóricos (PASI 75 y DLQI 0-1) podrían representar diferencias espurias. Es decir, tanto a corto como a largo plazo, se tiene que secukinumab y ustekinumab presentarían una eficacia similar en la población de la pregunta PICO. Asimismo, el análisis de los EA mostró que secukinumab y ustekinumab presentarían un perfil de seguridad similar en la población de la pregunta PICO. En vista que, tanto a corto como a largo plazo, no se presentaron diferencias respecto al riesgo de presentar desenlaces clave de seguridad, tales como EAS y DT por EA. Los resultados muestran que secukinumab y ustekinumab presentan un balance riesgo beneficio comparable en la población de la pregunta PICO del presente dictamen preliminar. En vista que, el impacto presupuestario sería menor con el uso de secukinumab que con ustekinumab (diferencia en alrededor de S/ 12,053.80, a favor de secukinumab), la aprobación de secukinumab sería la decisión más costo-oportuna para un sistema de salud público como EsSalud. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación ­ IETSI aprueba el uso de secukinumab para el manejo de los pacientes con psoriasis vulgar severa con falla terapéutica a terapia tópica, fototerapia, terapia sistémica convencional y terapia biológica anti-FNT disponibles en EsSalud.

Canadian Association of Gastroenterology Clinical Practice Guideline for the medical management of pediatric luminal Crohn's Disease

We aim to provide guidance for medical treatment of luminal Crohn's disease in children. We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.

Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Standard and biological treatment in large vessel vasculitis: guidelines and current approaches.

INTRODUCTION: Giant cell arteritis and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis. High doses of glucocorticoids are effective in inducing remission in both conditions, but relapses and recurrences are common, requiring prolonged glucocorticoid treatment with the risk of the related adverse events. Areas covered: In this article, we will review the standard and biological treatment strategies in large vessel vasculitis, and we will focus on the current approaches to these diseases. Expert commentary: The results of treatment trials with conventional immunosuppressive agents such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide have overall been disappointing. TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. Observational evidence strongly supports the use of anti-TNF-α agents and tocilizumab in Takayasu patients with relapsing disease. However biological agents are not curative, and relapses remain common.

Novel environment influences the effect of paradoxical sleep deprivation upon brain and peripheral cytokine gene expression.

Sleep loss increases inflammatory mediators in brain and peripheral tissues, but the mechanisms underlying this association are not fully understood. Male C57BL/6j mice were exposed to paradoxical sleep deprivation (PSD) for 24h using the modified multiple platform (MMP) technique (platforms over water) or two different controls: home cage or a dry platform cage, which constituted a novel environment. PSD mice exhibited increased IL-1ß and TNF-α pro-inflammatory gene expression in brain (hypothalamus, hippocampus, pre-frontal cortex), as well as in peripheral tissues (liver, spleen), when compared with home-cage controls. In addition, among PSD mice, TGFß1, an anti-inflammatory cytokine, was increased in pre-frontal cortex, liver, and spleen in conjunction with elevated serum corticosterone concentration relative to home-cage controls. However, these differences were nearly abolished when PSD mice were compared with control mice subjected to a dry MMP cage, suggesting that simply exposing mice to a novel environment can induce an acute inflammatory response.

Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa.

Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S., it predominantly occurs in African American men between 20-40 years of age. DC also occurs in other races and women more rarely. DC has been reported worldwide. Older therapies reported effective include: low dose oral zinc, isotretinoin, minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone, incision and drainage, dapsone, antiandrogens (in women), topical clindamycin, topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair removal lasers (800nm and 694nm), and surgical excision. Newer treatments reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but the number of reports is small, dosing schedules variable, and the long term follow up beyond a year is negligible; treatment failures have been reported. TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge to aggressive surgical treatment, but long term data is lacking. Non-medical therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and modern external beam radiation therapy. Studies that span more than 1 year are lacking. Newer pathologic hair findings include: pigmented casts, black dots, and "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness syndrome, Crohn disease and pyoderma gangrenosum. Older associations include arthritis and keratitis. DC is likely a reaction pattern, as is shown by its varied therapeutic successes and failures. The etiology of DC remains enigmatic and DC is distinct from hidradenitis suppurativa, which is shown by their varied responses to therapies and their histologic differences. Like HS, DC likely involves both follicular dysfunction and an aberrant cutaneous immune response to commensal bacteria, such as coagulase negative staphylococci. The incidence of DC is likely under-reported. The literature suggests that now most cases of DC can be treated effectively. However, the lack of clinical studies regarding DC prevents full understanding of the disease and limits the ability to define a consensus treatment algorithm.

The Relationship between Polymorphisms in Tumor Necrosis Factor (TNF) Genes and Changes in Bone Mineral Density after Hormone Therapy in Postmenopausal Korean Women / 대한골다공증학회지

OBJECTIVES: To determine the association between polymorphisms in tumor necrosis factor-alpha (TNF-alpha), and TNF-beta genes, and changes in bone mineral density (BMD) after hormone therapy (HT) in postmenopausal Korean women. MATERIALS & METHODS: The TNF-alpha G(-308)A, C(-857)T, C(-863)A, T(-1031)C, and TNF-beta A252G polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or Taqman assay in 218 postmenopausal Korean women receiving sequential HT for 1 year. Bone mineral density (BMD) at the lumbar spine and femoral neck was examined by dual energy X-ray absorptiometry. Serum levels of bone specific alkaline phosphatase (BAP), osteocalcin (OST), type I C-telopeptide breakdown products (CTX), parathyroid hormone (PTH), calcium, and phosphorus were measured using enzyme-linked immunosorbent assay (ELISA), immunoassay, and atomic absorptiometry, respectively. RESULTS: The TNF-alpha G(-308)A, C(-857)T, C(-863)A, T(-1031)C, and TNF-beta A252G polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or Taqman assay in 218 postmenopausal Korean women receiving sequential HT for 1 year. Bone mineral density (BMD) at the lumbar spine and femoral neck was examined by dual energy X-ray absorptiometry. Serum levels of bone specific alkaline phosphatase (BAP), osteocalcin (OST), type I C-telopeptide breakdown products (CTX), parathyroid hormone (PTH), calcium, and phosphorus were measured using enzyme-linked immunosorbent assay (ELISA), immunoassay, and atomic absorptiometry, respectively CONCLUSIONS: The TNF-alpha G(-308)A, C(-857)T, C(-863)A, T(-1031)C, and TNF-beta A252G polymorphisms are not associated with changes in BMD after HT in postmenopausal Korean women.

[Effects of Huangqi Guizhi Wuwu Decoction given by different administration methods on rats with frostbite and the mechanism].

OBJECTIVE: To establish a rat model of frostbite and to evaluate the effects of different administration methods of Huangqi Guizhi Wuwu Decoction (HGWD), a compound traditional Chinese herbal medicine for warming meridians to disperse cold, on rats with frostbite. METHODS: Frostbite in rats was induced by the method of soaking feet in hypothermia ethanol-water mixture. Levels of interleukin-6 (IL-6), tumor necrosis factor-beta (TNF-beta), thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) in serum of rats treated with different administration methods of HGWD, such as oral administration (Oral HGWD), soak (Soak HGWD), and oral administration plus soak (Oral-soak HGWD), were tested by enzyme-linked immunosorbent assay. RESULTS: IL-6, TNF-beta, TXB(2) levels were significantly higher (P<0.01) and 6-keto-PGFbeta level was lower (P<0.01) in serum of rats in the untreated group than in the normal control group. Compared with the untreated group, the level of IL-6 obviously decreased (P<0.05) in serum of the rats treated by oral HGWD, while no significant decrease (P>0.05) was observed in the soak HGWD group, and there was no interaction (P>0.05) between the two administration methods in regulating the level of IL-6. The levels of TNF-beta obviously decreased (P<0.01, P<0.05) in serum of the rats treated by oral and soak HGWD, and there was interaction between the two administration methods. The level of TNF-beta in the oral HGWD group was significantly lower than that in the soak HGWD group (P<0.01). Compared with the untreated group, level of TXB(2) in oral HGWD or soak HGWD group did not decrease significantly (P>0.05) and there was no interaction (P>0.05) between the two administration methods. The level of 6-keto-PGF(1alpha) was obviously increased (P<0.01) in serum of the rats treated by oral HGWD, while there was no significant decrease (P>0.05) in the soak HGWD group as compared with the untreated group, and there was interaction (P<0.05) between the two administration methods in regulating the level of 6-keto-PGF(1alpha). CONCLUSION: Rats with frostbite has immunologic dysfunction and a state of forming thrombus easily. The oral-soak HGWD can improve frostbite of local skin in rats. The therapeutic mechanism of HGWD may be to regulate the dysfunction of immune system and the imbalance of TXB(2)-PGF(1alpha).

An aqueous extract of green tea Camellia sinensis increases expression of Th1 cell-specific anti-asthmatic markers.

The present study provides evidence of the anti-asthmatic signaling activity of an aqueous fraction of green tea using specific in vitro and in vivo assays in an ovalbumin-induced asthmatic model. Mice sensitized to ovalbumin were orally administered an aqueous extract of Camellia sinensis. The lungs of these mice were then examined by hematoxylin and eosin staining and ELISA analysis to measure cytokine expression. The aqueous extract of Camellia sinensis exhibited potent anti-asthmatic activity by increasing the expression level of tumor necrosis factor-beta and interferon-gamma and decreasing the expression of anti-asthmatic cytokines in the lung. Together, these results indicate that the aqueous fraction of Camellia sinensis is effective in alleviating asthmatic symptoms by increasing the expression of Th1 cell-specific anti-asthmatic biomarkers.

[Leprosy: a paradigm for the study of human genetic susceptibility to infectious diseases]. / La lèpre: un paradigme pour l'étude de la prédisposition génétique aux maladies infectieuses.

Fifty years ago, the first identification of a non Mendelian genetic contribution to the development of a common infectious disease, i.e. the association between malaria and sickle-cell trait, was shown using a supervised approach which tests a limited number of candidate genes selected by hypothesis. Since then, the few genes that were convincingly associated with susceptibility to human infectious diseases were identified following the same strategy. The study of leprosy has contributed to modifying this way of thinking. In the absence of a satisfying experimental model and because of the impossibility to grow the causative agent in vitro, the candidate gene approach has turned out to be of limited interest. Conversely, positional cloning led to the identification of two major genes involved in the control of the disease, establishing for the first time the oligogenic nature of a human genetic contribution to an infectious disease. It is likely that these major results obtained in leprosy and the recent burst of genomic tools will make the genome-wide screening (functional or positional) the main strategy of dissection of the genetic susceptibility to many common infectious diseases.

Herpes simplex virus co-infection-induced Chlamydia trachomatis persistence is not mediated by any known persistence inducer or anti-chlamydial pathway.

Several inducers of chlamydial persistence have been described, including interferon-gamma (IFN-gamma), IFN-alpha, IFN-beta, and tumour necrosis factor-alpha (TNF-alpha) exposure, and iron, amino acid or glucose deprivation. A tissue-culture model of Chlamydia trachomatis/herpes simplex virus type-2 (HSV-2) co-infection indicates that viral co-infection stimulates the formation of persistent chlamydiae. This study was designed to ascertain whether co-infection-induced persistence is mediated by a previously characterized mechanism. Luminex assays indicate that IFN-gamma, IFN-alpha, and TNF-alpha are not released from co-infected cells. Semiquantitative RT-PCR studies demonstrate that IFN-beta, IFN-gamma, indoleamine 2,3-dioxygenase, lymphotoxin-alpha and inducible nitric oxide synthase are not expressed during co-infection. These data indicate that viral-induced persistence is not stimulated by any persistence-associated cytokine. Supplementation of co-infected cells with excess amino acids, iron-saturated holotransferrin, glucose or a combination of amino acids and iron does not restore chlamydial infectivity, demonstrating that HSV-2-induced persistence is not mediated by depletion of these nutrients. Finally, inclusions within co-infected cells continue to enlarge and incorporate C(6)-NBD-ceramide, indicating that HSV-2 co-infection does not inhibit vesicular transport to the developing inclusion. Collectively these data demonstrate that co-infection-induced persistence is not mediated by any currently characterized persistence inducer or anti-chlamydial pathway. Previous studies indicate that HSV-2 attachment and/or entry into the host cell is sufficient for stimulating chlamydial persistence, suggesting that viral attachment and/or entry may trigger a novel host pathway which restricts chlamydial development.

Black tea-induced decrease in IL-10 and TGF-beta of tumor cells promotes Th1/Tc1 response in tumor bearer.

Several lines of evidence support that impairment of host immune function by tumor may be related to several strategies of tumor escape from immunosurveillance. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice, the tumor cells secrete immunosuppressive cytokines, transforming growth factor beta (TGF-beta) and interleukin-10 (IL-10) that induce a general T helper cells type 2 (Th2) dominance dampening the T cytotoxic cells type 1 (Tc1) population. Interestingly, black tea at the antitumor dose of 2.5% significantly reduced TGF-beta and IL-10 in tumor cells in vivo, thereby preventing Th2 dominance in the tumor bearers and initiating a Th1/Tc1 response. Thus, apart from its anticancer activity, this popular beverage also rejuvenates cancer immunosurveillance by modulating cytokine profiles and establishing Th1/Tc1 dominance in the tumor-bearing host.

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines.

PURPOSE: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-alpha, and lymphotoxin-beta) or fibrogenic cytokines (transforming growth factor [TGF]-beta) during the same acute and chronic phases. METHODS AND MATERIALS: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. RESULTS: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-alpha, and lymphotoxin-beta) and the fibrogenic cytokine, TGF-beta, in cutaneous tissues at 21 days postradiation. CONCLUSION: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

[Effect of Acanthopanax senticosus injection on the activities of human tumor necrosis factor and natural killer cell in blood in the patients with lung cancer].

OBJECTIVE: To study the effect of Acanthopanax senticosus injection (ASI) on the activities of human tumor necrosis factor (TNF) and natural killer cell (NKC) in the patients with lung cancer and the underlying mechanism. METHOD: 73 cases with lung cancer were randomly divided into two groups, namely, the treatment group (n = 39) and observation group (n = 34); 61 cases with or without other diseases were respectively divided into control A (n = 30) and B (n = 31) groups. The patients in treatment group were injected with ASI for 21 days. The activities of human TNF and NKC and the levels of IgG, IgA and IgM were detected respectively. RESULT: After injection with ASI the activity of TNF-alpha in treatment group was comparable with that in the two control groups and was significant lower that that in observation group. The activity of TNF-beta and the levels of IgA, IgG and IgM were significantly higher than those in observation group and two control groups (P < 0.01). The activity of NKC was also remarkably higher than observation and two control groups. CONCLUSION: ASI can regulate the cellular immunity and factor, indicating that ASI can be used as an assistant drug to regulate the function of cellular immunity in the patients with lung cancer.

Enhancing effects of Scutellaria baicalensis and some of its constituents on TGF-beta1 gene expression in RAW 264.7 murine macrophage cell line.

Transforming growth factor beta1 (TGF-beta1) has been implicated as an inhibitor of cell proliferation and a potent inducer of apoptosis. Scutellaria baicalensis Georgi (SbG) has been widely used in Asia and recent investigations have shown that SbG has anticancer, antiviral, and anti-inflammatory effects. The aim of this study is to investigate the modulatory effect of SbG on TGF-beta1 gene expression. By using RAW 264.7 cell line as an in vitro model, the effects of SbG on TGF-beta1 gene expression were evaluated by ELISA, reverse-transcription polymerase chain reaction (RT-PCR) and quantitative PCR. Many inhibitors such as mitogen-activated protein kinase (MAPK) inhibitor (PD98059), p38-MAPK inhibitor (SB203580), NF-kappaB inhibitor (aspirin) and protein kinase C inhibitor (H7) were used to determine the possible signal transduction pathways. The results showed that crude extracts of SbG as well as its pure compounds, baicalin, baicalein and chrysin up-regulated TGF-beta1 gene expression on RAW 264.7 cells in a concentration-dependent manner. However, the flavonoid of SbG, wogonin, did not up-regulate TGF-beta1 expression on gene and protein levels on RAW264.7 cells. The facts that aspirin and H7 but not PD98059 and SB203580 blocked the enhancing effect suggested that NF-kappaB and PKC might be involved in baicalin-enhanced TGF-beta1 gene expression. We conclude that SbG up-regulates TGF-beta1 gene expression on RAW264.7 cells through NF-kappaB and PKC pathways and this might provide evidence to explain the therapeutic effect and potential adverse effects on the clinical use of Scutellaria baicalensis Georgi.

Differential lymphotoxin-beta and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury.

The liver regenerates after acute injury via hepatocyte cell division; during chronic injury, when hepatocyte replication is impaired or blocked, liver progenitor oval cells mediate liver regeneration. If both regeneration options are blocked in animal models, then liver failure and death ensues. The mechanisms underlying oval cell induction, proliferation, and subsequent liver regeneration remain poorly characterized. In particular, cell-signaling pathways that distinguish the alternative pathways are unknown. This study shows that in a mouse model, hepatic expression of lymphotoxin-beta (LTbeta) and interferon gamma (IFNgamma) transcripts is increased in response to the choline-deficient, ethionine-supplemented (CDE) diet, which induces oval cell-mediated liver regeneration. Oval cells express LTbeta and IFNgamma transcripts, contributing to the increased expression in the liver of mice fed the CDE diet. An attenuated oval cell response to such a diet was observed in LTbeta receptor-, LTbeta-, and IFNgamma-gene targeted mice. Loss of LTbeta and LTbeta receptor signaling reduced the number of oval cells expressing A6 and muscle pyruvate kinase. The lack of IFNgamma signaling reduced muscle pyruvate kinase(+), but not A6(+), oval cells. In contrast, partial hepatectomy suppressed LTbeta and IFNgamma transcripts. We also show that IFNgamma induces STAT-3 phosphorylation in an oval cell line. In conclusion, LTbeta, LTbeta receptor, and IFNgamma are involved in oval cell-mediated, but not hepatocyte-mediated, liver regeneration, and the absence of these pathways impairs the oval cell-dependent regenerative response.

TNF/LTalpha double knockout mice display abnormal inflammatory and regenerative responses to acute and chronic liver injury.

Following acute liver injury, hepatocytes divide to facilitate regeneration. However, during chronic injury, hepatocyte proliferation is typically blocked and repair is mediated through liver progenitor (oval) cells. Signalling of the p55 tumour necrosis factor (TNF) receptor is central to these processes. Two ligands for p55 are known: TNF and lymphotoxin-alpha (LTalpha). However, one study suggests that another exists that mediates liver injury following viral challenge. We have therefore investigated whether ligands other than TNF and LTalpha are required for liver regeneration following either acute or chronic injury. Wild-type and double TNF/LTalpha knockout (TNF-/-LTalpha-/-) mice were subjected to either partial hepatectomy (PHx) or a choline-deficient ethionine-supplemented (CDE) diet. Proliferating hepatocytes, oval cells and inflammatory cells were identified and quantified in liver sections by immunohistochemistry. Liver inflammatory cells were characterised by cell surface antigen expression. Liver damage and mortality were monitored. Both hepatocyte and oval cell proliferation was reduced in TNF-/-LTalpha-/- mice. Lymphocyte clusters were evident in all TNF-/-LTalpha-/- livers and were heterogeneous, comprising B and T lymphocytes. PHx evoked liver inflammation in TNF-/-LTalpha-/- but not wild-type mice, whereas no difference was apparent between genotypes in CDE experiments. Thus, TNF/LTalpha signalling mediates liver regeneration involving both hepatocytes and progenitor cells. The hyper-inflammatory response following PHx in TNF-/-LTalpha-/- animals, which is absent following CDE-induced injury, demonstrates that the two forms of liver injury evoke discrete inflammatory responses and provides a model in which such differences can be examined further.